Topical application of phenytoin or nifedipine-loaded PLGA microspheres promotes periodontal regeneration in vivo

Objectives: Gingival recession and alveolar bone loss are common manifestations of periodontitis. Periodontal regeneration is the ideal strategy for rehabilitating periodontal tissue defects and preventing tooth loss. The present study examined whether localized, topical application of gingival overgrowth-inducing drugs, phenytoin, nifedipine or cyclosporine, induces periodontal regeneration. Methods: Polylactic-co-glycolic acid (PLGA) was used as the carrier for preparation of phenytoin, nifedipine or cyclosporine-loaded PLGA microspheres, using an oil-in-water emulsification technique. The drug-loaded microspheres were delivered to periodontal defects created on alveolar ridges mesial to the first maxillary molars of Sprague-Dawley rats. After eight weeks, the operation area in each rat, including the maxillary molars and periodontal tissues, was harvested and evaluated by micro-computed tomography, histochemical and immunohistochemical analyses. Results: Physical parameters representative of periodontal regeneration, including the length of new alveolar bone (p < 0.01) and the area of new alveolar bone (p < 0.01) were significantly improved in the phenytoin group. Compared to other groups, the phenytoin group demonstrated increased expression of COL-1, VEGF-A, osteoblast and osteoclast markers (BMP-2, TGF-β1, OCN and TRAP staining), as well as decreased expression of MMP-8. Conclusions: Results of the present study provided new evidence that localized, controlled release of phenytoin confers therapeutic benefits toward gingival recession and alveolar bone loss. Phenytoin appears to be a promising drug that promotes periodontal regeneration.